Expression of NF-κB and IκB proteins in skeletal muscle of gastric cancer patients

Abstract 

The mechanisms eliciting cancer cachexia are not well understood. Wasting of skeletal muscle is problematic because it is responsible for the clinical deterioration in cancer patients and for the ability to tolerate cancer treatment. Studies done on animals suggest that nuclear factor of kappa B (NF-κB) signalling is important in the progression of muscle wasting due to several types of tumours. However, there are no published studies in humans on the role of NF-κB in cancer cachexia. In this project, we studied the rectus abdominis muscle in patients with gastric tumours (n=14) and in age-matched control subjects (n=10) for markers of NF-κB activation. Nuclear levels of p65, p50 and Bcl-3 were the same in both groups of subjects. However, phospho-p65 was elevated by 25% in the muscles of cancer patients. In addition, expression of the inhibitor of kappa B alpha (IκBα) was decreased by 25% in cancer patients. Decreased expression of IκBα reflects its degradation by one of the IκBα kinases and is a marker of NF-κB activation. Interestingly, there was no correlation between the stage of cancer and the extent of IκBα decrease, nor was there a correlation between the degree of cachexia and decreased IκBα levels. This suggests that the activation of NF-κB is an early and sustained event in gastric cancer. The work implicates the NF-κB signalling in the initiation and progression of cancer cachexia in humans and demonstrates the need for additional study of this pathway; it also recommends NF-κB signalling as a therapeutic target for the amelioration of cachexia as has been suggested from studies done on rodents.

Keywords: Bcl-3, NF-κB, IκBα, Skeletal muscle, Cancer cachexia, Gastric cancer patients